HIV-1 negative men reporting anal sex with another man in the past year were randomized to initiate once-daily TDF (300mg) or placebo at enrollment or after a 9-month delay. Quarterly visits included HIV testing, risk-reduction counseling, and assessments of biomedical and behavioral safety, adherence, and acceptability. Bone density (DEXA) was assessed in San Francisco.

No grade 3 or 4 creatinine elevations were observed. A total of 27 protocol-defined serious adverse events occurred, 16 on TDF and 11 on placebo (p=0.56). Among 186 San Francisco participants who had DEXA scans, 11 discontinued drug (per protocol) for >5% decrease in bone density (total hip or spine) from baseline (8[8%] on TDF, 3[3%] on placebo; p=0.21). Seven participants became HIV infected; four were placebo recipients (including one seronegative at enrolment but subsequently found to be acutely infected); three were in the delayed arm and seroconverted before starting study drug.

Conclusions: No significant biomedical safety issues were identified. This study was not designed to detect efficacy of TDF in preventing HIV infection. Adequately powered efficacy trials are underway to address this question.

Tenofovir Pre-Exposure Prophylaxis Against HIV Found Safe

MedPage Today
Published: July 25, 2010

Action Points

* Explain that researchers are investigating whether prophylaxis with an antiretroviral drug might prevent transmission of HIV in high-risk groups.

* Note that this study suggests that such an approach is safe but caution that it's still not known if it would prevent transmission; that research must still be done.

* Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

VIENNA -- Treating men at high risk of HIV with an antiretroviral drug -- as a preventive measure while they remain HIV-negative -- appears to be safe, a researcher said here.

The drug -- 300 mg daily of tenofovir (Viread) -- was generally well tolerated in a cohort of 373 men who have sex with men, according to Lisa Grohskopf, MD, of the CDC.

While there were no new HIV cases among those taking the drug and six cases among men getting either placebo or no treatment, it's too early to say that the intervention works, Grohskopf told a late-breaking session at the International AIDS Conference.

Pre-exposure prophylaxis -- or PrEP -- is being studied as a way to prevent transmission of the disease in several countries, but researchers are concerned about the morbidity associated with giving powerful medications to people who are not yet sick.

They also fear so-called "behavioral disinhibition" among those receiving PrEP -- risky changes in behavior because of the supposed HIV-protective effect of the medication.

To test the validity of those fears, Grohskopf and colleagues enrolled a group of men who have sex with men in Atlanta, Boston, and San Francisco; 73% were white and 15% were African American, with a median age of 39.

Half of the cohort was immediately randomized to get either the drug or a placebo, while the remainder went through routine study procedures for nine months -- including HIV testing and risk reduction counseling -- before being randomized to drug or placebo.

Over the 24 months of the study, Grohskopf reported, there were 2,584 adverse events among the participants, most of those events mild in nature. There were 30 serious adverse events among 18 participants and one death, judged to be unrelated to the study.

The most common adverse events were included diarrhea, back pain, headache, and depression, but only back pain was significantly different (at P=0.04) between the groups, with 25 reports among those taking tenofovir and 12 among those on placebo.

There were no significant differences between the study groups in grade three or four adverse events, nor were there differences in the rates of creatinine elevation or hypophosphatemia, she said.

Overall, there were seven seroconversions, but one infection was judged to have occurred just at the start of the study -- the patient was HIV-negative on a screening test but tested positive a month later.

Three incident cases of HIV occurred in the placebo arm and three occurred among men whose randomization was delayed. There were no cases among patients on tenofovir, but Grohskopf cautioned that the study was not designed to test the efficacy of the intervention.

"No conclusions can be drawn" about efficacy from the findings, she said, since they could well be due to chance.

Grohskopf said she and colleagues are still analyzing data about changes in risk behavior, but so far, she said, they have seen no evidence of behavioral disinhibition.

That's an important issue, according to Maria Prins, MSc, an epidemiologist at the Amsterdam public health service, who was not part of the study but moderated the session at which it was presented.

"After the introduction of HAART, we began to see increases in risky behavior, especially among homosexual men," she told MedPage Today. "So it was good to see the risk behavior was stable" in this study.

The biomedical data is also reassuring, she said. "It's important to show that there were no differences between the groups," she said. "We'll need that (information) to get the phase III studies going."

The study was supported by the CDC and the NIH. Grohskopf is an employee of the CDC.